Methods and compositions for improving feed efficiency of ruminants using poyhydric alkanol haloacetaldehyde hemiacetals

ABSTRACT

POLYHYDRIC ALKANOL HALOACETALDEHYDE HEMIACETALS ARE POTENT INHIBITORS OF METHANOGENESIS IN THE RUMINANT ANIMAL. CONSEQUENTLY THESE CHEMICAL AGENTS IMPROVE THE FEED EFFICIENCY IN RUMINANTS AT LEVELS WHICH DO NOT HAVE THERAPEUTIC OR GENERAL ANTIFERMENTATION EFFECTS IN THE ANIMAL. THE MOST USEFUL AND REPRESENTATIVE COMPOUND IS PENTAERYTHRITOL TETRACHLORAL HEMIACETAL. METHODS OF ADMINISTRATION, FEED COMPOSITIONS AND PREMIXES CONTAINING SAID INHIBITORS ARE DESCRIBED.

United States Patent US. Cl. 424-342 16 Claims ABSTRACT OF THE DISCLOSURE Polyhydric alkanol haloacetaldehyde hemiacetals are potent inhibitors of methanogenesis in the ruminant ammal. Consequently these chemical agents improve the feed efficiency in ruminants at levels which do not have therapeutic or general antifermentation effects in the annual. The most useful and representative compound 1s pentaerythritol tetrachloral hemiacetal. Methods of administration, feed compositions and premixes containing sa1d inhibitors are described.

This is a continuation-in-part application of our earlier but pending applications Ser. No. 881,868, filed Dec. 3, 1969 and Ser. No. 881,915, filed Dec. 3, 1969 now US. Pat. No. 3,615,649.

This invention relates to advantageous new methods and compositions for improving the feed efiiciency in ruminant animals using specified polyhydric alkanol haloacetaldehyde hemiacetals as active ingredients. These methods and compositions use oral administration of effective but not noxious quantities of the active ingredients to inhibit methanogenesis in the rumen itself. One result of these inhibitors of methane is an apparent decrease in gaseous loss of carbon and hydrogen during fermentation and alteration of rumen metabolism as, for example, a shift toward producing more desirable fatty acids for growth especially propionic and butyric acids. These are more readily utilized by the ruminant to increase the efiiciency of rumen digestion of feed to give more weight gain on the same or less ingested feed. Details of the supposed mechanism of action and testing procedures are outline in our previous pending applications referred to above.

We have now discovered that certain polyhydric alkanol haloacetaldehyde hemiacetals have extremely good activity, are of unusually low cost, are palatable to the animal, and form acceptable feed and premix compositions.

The active ingredients are represented by the following structural formula:

in which n is an integer of from 0 to 4; m is an integer of from 2-6; X is hydrogen, bromo or chloro at least two of which are bromo or chloro; and R is a straight or branched alkane chain of 2-6 carbon atoms. The sum of n plus m should for practical reasons be no larger than 6.

The preferred compounds are those in which n is 0, m is 3-6, X is chloro and R contains 5-6 carbon atoms. A particularly useful and valuable compound is pentaerythritol tetrachloral hemiacetal.

One skiled in the art will realize that the O'-lower acyl or O-lower alkyl derivatives of these compounds can be 3,745,221 Patented July 10., 1973 "ice optionally prepared such as those derived from alkanes of up to 6 carbons. Also the alkanc skeleton can be enlarged by optional methylene groups or may be cyclic. None of these or other modifications are particularly advantageous over those described since a high halogen content and low cost of chemical are vital to the commercial aspects of this invention.

The active ingredients of this invention are prepared by the methods described in US. Pat. No. 2,784,237. Briefly the known alkanol and the desirable mole equivalent amount of haloacetaldehyde are reacted in an unreactive solvent or preferably no solvent usually at reflux temperature until reaction is complete. In the latter case if the product is a solid, the molten product is then poured onto trays, cooled, and broken up. Other methods of synthesis are detailed in J. Indian Chem. Soc. 13, 118 (1936). Most of the active ingredients of this invention are solid glasses or high boiling viscous liquids. The solid chemicals are preferred since they are easily powdered. The liquid products can be best used as an additive to feed in the form of a premix mixed then used promptly.

In the active chemical ingredient, mixtures of variously substituted alkanols may be used since it is often more economical to run the reaction and not purify the resulting product completely. The exact number of halohemiacetal groups present is immaterial if the chemical composition of the active ingredient is reproducible according to standard analytical procedures. Chlorine content is a most useful analytical tool. In practice the compounds in which all the hydroxyl groups, up to six, are reacted to form hemiacetal derivatives are preferred as the most active and most economical compounds to be used in this invention. However, as is clear above, less than all the available hydroxyl groups may be converted to halohemiacetal derivatives. In practice at least two per molecule of polyhydric alkanol and preferably four to six polyhalohemiacetal groups are present.

Among the more useful compounds to be active ingredients in this invention are mannitol chloral hemiacetal, sorbitol hexachloral hemiacetal, mannitol hexachloral hemiacetal, mannito tetrachlora hemiacetal, glycerol trichloral hemiacetal, glycerol tribromal hemiacetal, propylene glycol dichoral hemiacetal and especially pentaerythritol tetrachloral hemiacetal.

The above derivatives known to the art which are stable nonvolatile solids are of course preferred.

The chemical ingredients are incorporated into feed or feed premix compositions in effective but nontoxic and nontherapeutic quantities which increase feed efiiciency. The compositions are then fed to ruminant animals as usual in the agricultural art mostly ad libitum.

The ruminant feeds most generally used in conjunction with the method of this invention are either the roughage feeds such as silage or various commercial grain mixtures commonly used in ruminant animals, that is, in cattle or sheep. The amount of additive used to supplement such feeds will be an amount suflicient to improve the feed efiiciency of the animal but not to have a pharmacodynamic or otherwise toxic or noxious effect. For example, in the broad range of about 10 g. to 2 kg. of additive per ton of feed (about 0=.00l-0.2%) preferably from about 50-600 'g./ton. An average sheep will ingest about 3-4 lbs. of feed daily. An average cow about 20- 25 lbs. Therefore, the broad range of dosage for ruminants (sheep to cows) is roughly about 50 mg.7 g. per day.

As a specific preferred example, pentaerythritol tetrachloral hemiacetal (PTH) may be used at the rate of from about 50-500 g./ton of feed for sheep preferably about 200-400 g./ton. In using'ingredients having fewer haloacetal groups, i.e., a lower chlorine or bromine content, larger amounts in the range are used, more groups lower amounts. It will be noted that the amount of ac-.

tive ingredient ingested per day per ruminant is much lower than the therapeutic ranges such as the sedative effects noted in Pat. No. 2,784,237 for these compounds.

For commercial use, the active ingredients are most readily used as premix formulations in which the chemical is distributed uniformly throughout a standard animal feed carrier in an amount to give active levels of chemical ingredient at tonnage amounts as described above when diluted to whole feed. This premix or concentrate is mixed with either a normal or a special fattening diet of the ruminant as desired. Examples of such carriers are soybean meal, corn oil, ground corn, barley, wheat, mineral mixtures such as vermiculite, diatomaceous earth, corn gluten meal, corn distillers solubles or soyflour. The active ingredient will be in amounts to satisfy the criteria set forth above for whole feed. The active ingredient will usually be present in from about 5-75% by weight of the premix composition depending largely on the physical properties and activity of the active ingredient. If the chemical is a liquid, it may be adsorbed on a carrier such as vermiculite prior to mixing. If the chemical is a solid glasslike material, it usually is powdered using a minimum of heat source.

The animal feeds themselves may also contain cellulosic roughage such as cellulose, hay, straw, corn stalks, cotton seed hulls, oats, barley and cereal brans; natural oils such as animal fats, fish oils, safflower oil, peanut oil and cottonseed oil, antioxidants, minerals, vitamins; antibiotics; anthelmintics; and other appropriate medicaments.

A typical prepared animal feed is as follows:

An example of a suitable premix is as follows:

Pentaerythritol tetrachloral hemiacetal (PTH) 200 g. Ground yellow corn To 3 lb.

Another might be a mixture of active ingredient and vermiculite.

In the field the active ingredients may be administered by means of salt or molasses blocks. A typical block may be prepared using the following conditions:

Ingredient: Weight percent Dried cane molasses 44.54 Ground soybean hulls 24.90 Pentaerythritol tetrachloral hemiacetal (PTH) 5.00 Granulated salt 21.59 Trace minerals and vitamins 0.20 Stabilized animal fat 1.11 Moisture 2.66

The method of this invention comprises allowing the cattle or sheep to graze or be fed ad libitum on the supplemented rations or to be hand fed on a regular schedule.

Normally we have found feed efficiency increases of from about 10-15% using normal fattening diets and conditions.

The ability of the polyhydric alkanol polyhalohemiacetal derivatives of this invention to improve feed utilization in ruminants is primarily evaluated by means of a test which measures in vitro methane gas production plus total gas production as an indicator of the rate of fermentation of feedstulfs by microorganisms of the rumen. Rumen fluid is obtained from a fistulated animal and is filtered through six layers of cheesecloth. The fluid (75 ml.) is then added to 2.4 g. of experimental ration as substrate. Test compound is then added and the mixture is incubated for 3 hours. Test compound may be added as such or, particularly when used in quantities as small as 10 p.p.m. or less, suspended or dissolved in a solvent such as water or ethanol. At the end of the test period, the trapped gases are sampled by hypodermic needle from the flask and run through a gas partitioner (column chromatography) which separates and quantitates the components. The liquids (volatile fatty acids, etc.) are analyzed by gas liquid chromatography. Among the products measured are carbon dioxide, lactic acid, ethanol, hydrogen, ammonia nitrogen and fatty acids having from 2 to 6 carbon atoms. Reduction in the percent methane produced of 20% is considered significant. However, with compounds used in the present invention, reduction of 100% Without reduction of overall fermentation is not uncommon. Ability of a particular compound to reduce the amount of methane generated without adversely reducing the overall rate of fermentation is determined by comparing the total (nmoles/ml.) volatile fatty acids produced in control systems with those containing test compound. Also most significant is the distribution of fatty acids obtained.

The effect of the polyhydric alkanol polyhaloacetal derivatives of this invention in reducing methane production without causing a reduction in the rate of overall fermentation at effective concentrations, when tested by the above procedures, is shown by the data below.

A predetermined molar or percent concentration of test compound in water or ethanol was administered usually in 0.1, 0.5 or 1.0 cc. portions as described above. The data in Table I is, for parts of active ingredient per amount of rumen fluid, i.e., parts per million with resulting significant methane inhibition. Generally speaking, p.p.m. equals 0.01% of diet or 90.8 g./ton of feed.

TABLE I Percent methane Compound reduction P.p.m.

Glycerol triehloral hemiacetal- 1,2-propylene glycol dlehloral heml acetal Mannitol hexachloral hemiacetal.

Pentaerythritol tetraehloral hemiacetal. 100

TABLE II Molar percent Treated Controls 15 to 18 19 to 22: Remainder to 100%- Remainder to 100%.

68 to 72.. 67 to 74.

The in vitro data presented above was confirmed by specific in vivo tests as follows:

Each dose level represents a test group of four head of pinhole fistulated sheep. The animals were fed the additive (PTH) mixed with morning and evening feed in quantities so that 90% ad libitum amounts were administered. The sh'eep would eat all the supplemented feed in one hour. The results ran for a 7-day period.

Samples were withdrawn from the rumen 4-5 hours after the morning feeding and again 15-18 hours after the evening feeding. The ration was all roughage ration.

Gas Analysis (Corrected) [PTH mixed in feed at 500 p.p,m.]

Control Treated Volatile Fatty Acid Analysis [PTH mixed in feed at 500 p.p.m.]

Control Treated Component:

Acetate, 01-... Propionate, Ca. Butyrate, 04.- Valerate C5 Total moles/ml As expected, the ratio of C /C +C narrows (decreases) from 3.30 for control to 1.49 for treated group.

This data in sheep using pentaerythritol tetrachloral acetal confirms the in vitro results present.

The in vivo results above were confirmed by actually sampling the methanogenesis inhibition in 5 randomly chosen sheep in the feeding trials described hereafter:

At 400 g./ton of pentaerythritol tetrachloral hemiacetal (PTH):

Percent methane Animal No.

Control. 1

Feeding trials using various dose levels of pentaerythritol tetrachloral hemiacetal were carried out on West Texas feeder lambs under feedlot conditions. The control consisted of three pens of lambs each. The treated lambs also consisted of three pens of 10 lambs each at each dose level. The data presented is cumulative after 60 days treatment. The experimental ration used was:

Percent w./ W. Mixed ground hay 13% 40.0. Ground corn 44.0. Soybean meal 44% 7.0. Dried molasses 87% 8.0. Dicalcium phosphate 0.5. Trace minerals a- 0.5. Vitamin A 30,000 units/gm. 20 g./ton. Vitamin D 16,000,000 units/gm 8.5 g./ton.

The following results were obtained:

Average net feed consumed Average Average wt. gain food/gain Controls 200 g./ton 400 g./ton

animals an effective but nontoxic and nontherapeutic quantity of an active ingredient comprised of a polyhydric alkanol haloacetaldehyde hemiacetal derivative of the formula:

in which:

n is an integer of from 0-4;

m is an integer ofirom 2-6; 7

X is hydrogen, bromo or chloro at least two of which are bromo or chloro; and

R is a straight or branched alkane chain of 2-6 carbon atoms, the sum of n plus m being a maximum of 6, said quantity being from the daily dosage of about 50 mg. -7 g. per ruminant animal.

2. The method of claim 1 in which n is 0, m is 3-6, and X is chloro or bromo.

3. The method of claim 1 in which the quantity of polyhydric alkanol haloacetaldehyde hemiacetal is from about 10 g. to about 2 kg. per ton of feed.

4. The method of claim 1 in which the quantity of active ingredient is from about 50-600 g. per ton of feed.

5. The method of claim 1 in which the quantity of active ingredient is about 200 g. per ton of feed.

6 The method of claim 1 in which the active ingredient is pentaerythritol tetrachloral hemiacetal.

7. The method of claim 6 in which the active ingredient is present in the feed at the rate of about -400 g./ton of feed.

8. The method of claim 6 in which the active ingredient is present in the feed at the rate of about 200 g./ ton of feed.

9. An animal feed supplemented by the quantity of polyhydric alkanol haloacetaldehyde hemiacetal derivative of claim 1.

10. An animal feed supplemented by the quantity of polyhydric alkanol haloacetaldehyde hemiacetal derivative of claim 3.

11. An animal feed supplemented by the quantity of polyhydric alkanol haloacetaldehyde hemiacetal derivative of claim 4.

12. An animal feed supplemented by the quantity of polyhydric alkanol haloacetaldehyde hemiacetal derivative of claim 6.

13. A premix feed containing the quantity of polyhydric alkanol haloacetaldehyde hemiacetal derivative of References Cited UNITED STATES PATENTS 3/1957 Bruce 2606l5 A OTHER REFERENCES Journal of Dairy Science, vol. 51, No. 6, pp. 882-887, 1968, Prins et al.

Journal of Bacteriology, vol. 94-, No. 1, pp. 171-175, July 1967, Bauchop, T.

NORMAN YUDKOFF, Primary Examiner K. P. VAN WYCK, Assistant Examiner US. Cl. X.R. 

